The composition and structure of metalloenzymes as these relate to their function continues as our primary objective in the exploration of the physical and chemical basis of biological specificity proposed herein. Several well characterized metalloenzymes, including carboxypeptidase, thermolysin, alkaline phosphatase, alcohol dehydrogenase, as well as the recently purified nucleic acid polymerases from E. gracilis are studied both to discern their mechanism of action as well as to provide general insight into the mode of interaction of metals with enzymes and proteins. Using these systems as models, new spectral and chemical probes are sought as tools for the study of structure and function of these proteins in solution. Concomitantly, utilizing new, highly sensitive spectroscopic techniques together with spectral and chemical probes, the separation and identification of metal-dependent components, including neoplastic disease are being undertaken. Studies will be carried out with both microorganisms as well as cultured human cells with the view toward establishing useful parallels with which to design further experiments in both systems. The participation of zinc, now firmly established, and other metals as well, in the mechanism of action of both viral reverse transcriptases as well as numerous other enzymes involved in normal nucleic acid metabolism will continue to be explored in order to gain further insight into the mechanism of viral oncogenicity in animals.